Pancreas Pathology of Latent Autoimmune Diabetes in Adults (LADA) in Patients and in a LADA Rat Model Compared With Type 1 Diabetes
Pancreas Pathology of Latent Autoimmune Diabetes in Adults (LADA) in Patients and in a LADA Rat Model Compared With Type 1 Diabetes
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DOI：
10.2337/db19-0865
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发表时间：
2020-04-01
期刊：
影响因子：
7.7
通讯作者：
Lenzen, Sigurd
中科院分区：
文献类型：
--
作者：
Joerns, Anne;Wedekind, Dirk;Lenzen, Sigurd
大约 10% 的 2 型糖尿病患者患有成人潜伏性自身免疫性糖尿病 (LADA)。本研究对 LADA 患者内分泌胰腺的病理学进行了系统评估，并在模拟 LADA 患者特征的第一个大鼠模型中进行比较。通过免疫组织化学分析人和大鼠胰腺中的免疫细胞浸润成分，通过原位 RT-PCR 和激光显微切割胰岛的定量实时 PCR 分析促炎细胞因子、增殖标记物增殖细胞核抗原 (PCNA)、抗炎细胞因子白细胞介素 (IL) 10、凋亡标记物 caspase 3 和 TUNEL 以及胰岛素的基因表达。人类和大鼠 LADA 胰腺在免疫细胞浸润方面表现出胰腺面积的差异，并且巨噬细胞和 CD8 T 细胞数量与胰岛浸润中巨噬细胞之间的比率发生变化。基因表达分析显示，由于 IL-1 β 的增加和肿瘤坏死因子 α 的减少，比率发生了变化。 LADA 情况下 IL-10、PCNA 和胰岛素表达增加，而 caspase 3 基因表达减少。对人类和大鼠 LADA 胰腺的潜在病理学分析得出了相同的结果，得出这样的结论：LADA 是高龄患者中一种较温和的自身免疫性糖尿病。
Approximately 10% of patients with type 2 diabetes suffer from latent autoimmune diabetes in adults (LADA). This study provides a systematic assessment of the pathology of the endocrine pancreas of patients with LADA and for comparison in a first rat model mimicking the characteristics of patients with LADA. Islets in human and rat pancreases were analyzed by immunohistochemistry for immune cell infiltrate composition, by in situ RT-PCR and quantitative real-time PCR of laser microdissected islets for gene expression of proinflammatory cytokines, the proliferation marker proliferating cell nuclear antigen (PCNA), the anti-inflammatory cytokine interleukin (IL) 10, and the apoptosis markers caspase 3 and TUNEL as well as insulin. Human and rat LADA pancreases showed differences in areas of the pancreas with respect to immune cell infiltration and a changed ratio between the number of macrophages and CD8 T cells toward macrophages in the islet infiltrate. Gene expression analyses revealed a changed ratio due to an increase of IL-1 beta and a decrease of tumor necrosis factor-alpha. IL-10, PCNA, and insulin expression were increased in the LADA situation, whereas caspase 3 gene expression was reduced. The analyses into the underlying pathology in human as well as rat LADA pancreases provided identical results, allowing the conclusion that LADA is a milder form of autoimmune diabetes in patients of an advanced age.